Frontiers in Immunology (Nov 2021)

A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation

  • Henry Y. Lu,
  • Henry Y. Lu,
  • Robert Sertori,
  • Alejandra V. Contreras,
  • Mark Hamer,
  • Melina Messing,
  • Melina Messing,
  • Kate L. Del Bel,
  • Elena Lopez-Rangel,
  • Edmond S. Chan,
  • Wingfield Rehmus,
  • Joshua D. Milner,
  • Kelly M. McNagny,
  • Kelly M. McNagny,
  • Anna Lehman,
  • David L. Wiest,
  • Stuart E. Turvey,
  • Stuart E. Turvey

DOI
https://doi.org/10.3389/fimmu.2021.788278
Journal volume & issue
Vol. 12

Abstract

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B-cell lymphoma/leukemia 11B (BCL11B) is a C2H2 zinc finger transcription factor that is critically important for regulating the development and function of a variety of systems including the central nervous system, the skin, and the immune system. Germline heterozygous variants are associated with a spectrum of clinical disorders, including severe combined immunodeficiency as well as neurological, craniofacial, and dermal defects. Of these individuals, ~50% present with severe allergic disease. Here, we report the detailed clinical and laboratory workup of one of the most severe BCL11B-dependent atopic cases to date. Leveraging a zebrafish model, we were able to confirm a strong T-cell defect in the patient. Based on these data, we classify germline BCL11B-dependent atopic disease as a novel primary atopic disorder.

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